1. Field of the Invention
The present invention relates to topical pharmaceutical compositions comprising a pharmaceutically active agent, laurocapram, and one or more diols, particularly propylene glycol. The invention further relates to the use of the topical pharmaceutical compositions.
2. Related Art
A number of patents disclose compounds which enhance the penetration of physiologically active agents through the skin. See U.S. Pat. Nos. 4,122,170, 4,316,893, 4,444,762, 4,886,783, and 5,834,010.
U.S. Pat. No. 4,552,872 discloses topical pharmaceutical compositions comprising a pharmaceutically active corticosteroid together with a penetration enhancing vehicle containing a C.sub.3 -C.sub.4 diol, and a cell-envelope disordering compound such as oleic acid. The vehicle is substantially free of saturated, straight chain C.sub.16 -C.sub.20 alcohols and C.sub.4 -C.sub.20 mono- or dicarboxylic acids.
U.S. Pat. No. 4,557,934 discloses topical pharmaceutical compositions containing a pharmaceutically active agent, the penetrating enhancing agent 1-dodecylazacycloheptan-2-one (laurocapram), in combination with certain C.sub.3 -C.sub.4 diols. A preferred diol is propylene glycol. Preferred pharmaceutically active agents include corticosteroids such as triamcinolone acetonide, vitamins, antifungal agents, blood calcium regulators, etc.
U.S. Pat. Nos. 4,552,872, and 4,557,934 also teach that certain straight chain, saturated C.sub.16 -C.sub.20 normal fatty alcohols may interfere with penetration of the pharmaceutically active agents in the diol formulations, particularly, the propylene glycol formulations, and should be avoided if such interference is too great. In particular, the patents teach that cetyl (C.sub.16) and stearyl (C.sub.18) n-alcohols are capable of significant interference with the penetration enhancement of the formulation. In a preferred embodiment, the compositions are substantially free of such compounds and preferably contain less than 0.5% of cetyl or stearyl alcohol. Example 9 of the '934 patent shows that the skin penetration of the pharmaceutically active agent triamcinolone acetonide from a propylene glycol vehicle is reduced 39% upon the addition of cetyl alcohol at a concentration of 3% by weight.
Surprisingly, it has now been discovered that topical formulations comprising significant amounts of a pharmaceutically active agent such as a corticosteroid, cetyl alcohol, stearyl alcohol, laurocapram and a diol, preferably propylene glycol, are very effective in treating dermatological conditions.